PEGylated dendritic polyglycerol conjugate targeting NCAM-expressing neuroblastoma: Limitations and challenges

Laura Isabel Vossen, Ela Markovsky, Anat Eldar-Boock, Harald Rune Tschiche, Stefanie Wedepohl, Evgeny Pisarevsky, Ronit Satchi-Fainaro, Marcelo Calderón

Research output: Contribution to journalArticlepeer-review

Abstract

Neural cell adhesion molecule (NCAM) is found to be a stem-cell marker in several tumor types and its overexpression is known to correlate with increased metastatic capacity. To combine extravasation- and ligand-dependent targeting to NCAM overexpressing-cells in the tumor microenvironment, we developed a PEGylated NCAM-targeted dendritic polyglycerol (PG) conjugate. Here, we describe the synthesis, physico-chemical characterization and biological evaluation of a PG conjugate bearing the mitotic inhibitor paclitaxel (PTX) and an NCAM-targeting peptide (NTP). PG-NTP-PTX-PEG was evaluated for its ability to inhibit neuroblastoma progression in vitro and in vivo as compared to non-targeted derivatives and free drug. NCAM-targeted conjugate inhibited the migration of proliferating endothelial cells, suggesting it would be able to inhibit tumor angiogenesis. The targeting conjugate provided an improved binding and uptake on IMR-32 cells compared to non-targeted control. However, these results did not translate to our in vivo model on orthotopic neuroblastoma bearing mice.

Original languageEnglish
Pages (from-to)1169-1179
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number4
DOIs
StatePublished - Jun 2018

Keywords

  • Neural cell adhesion molecule
  • Neuroblastoma
  • Paclitaxel
  • Polyglycerol
  • Polymer-drug conjugates
  • Polymeric nanomedicines

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